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Celltex Therapeutics Corporation-FDA Warning Letter- 9-24-12

Celltex Therapeutics Corporation-FDA Warning Letter- 9-24-12

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Published by kehills
FDA Warning Letter to CellTex
FDA Warning Letter to CellTex

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Published by: kehills on Oct 22, 2012
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10/16/12 2012 > Celltex Therapeutics Corporation 9/24/121/6www.fda.gov/ICECI/EnforcementActions/WarningLetters/2012/ucm323853.htm
Celltex Therapeutics Corporation 9/24/12
Department of Health and Human Services
Public Health ServiceFood and Drug Administration Center for Biologics Evaluationand Research1401 Rockville PikeRockville, MD 20852-1448
 September 24, 2012CBER-12-10 
David G. EllerChief Executive Officer and PresidentCellTex Therapeutics Corporation12621 W. Airport Blvd., Suite 800Sugarland, TX 77478Dear Mr. Eller: During an inspection of your firm, CellTex Therapeutics Corporation, located at 12621 W. Airport Blvd.,Suite 800, Sugarland, Texas 77478, conducted between April 16 and April 27, 2012, the Food and DrugAdministration (FDA) determined that your firm receives adipose tissue (aka lipoaspirate) that has beenrecovered from autologous donors. Using
, your firm isolates cells from the lipoaspirate, andselects and expands through cell culture, adipose derived mesenchymal stem cells (AdMSC). Theautologous product is administered to patients by
for a wide variety of indications. Ourinvestigation of your firm further determined that your firm promotes your process and the use of  AdMSC to physicians by encouraging physicians to enrollpatients in one of your clinical trials. Yourprotocols entitled,
both explain that patients havean opportunity to be enrolled in these clinicaltrials if they are presently diagnosed with an
forwhich there is hypothesized or demonstratedclinical benefit for the
of the AdMSC product. CellTex’s product is a human cell, tissue, or cellular and tissue-based product (HCT/P) as defined in 21 CF1271.3(d). However, this product does not meet all of the criteria in 21 CFR 1271.10(a) and therefore isnot regulated solely under section 361 of the Public Health Service Act (PHS Act) [42 U.S.C. 264] and theregulations in 21 CFR Part 1271. Specifically, your processing with
alters the original relevantcharacteristics of the adipose tissue relating to the tissue’s utility for reconstruction, repair, orreplacement. Therefore, your processing does not meet the definition of minimal manipulation forstructural tissue such as adipose tissue as described in 21 CFR 1271.3(f)(1). Furthermore, your firm’sprocess of tissue culture, expansion and passaging also fails to meet the definition of minimal manipulatiofor structural tissue in 21 CFR 1271.3(f)(1). As a result, the CellTex product does not meet the criterion in21 CFR 1271.10(a).
Inspections, Compliance, Enforcement, and Criminal Investigations
Home Inspections, Compliance, Enforcement, and Criminal Investigations Enforcement Actions Warning Letters
10/16/12 2012 > Celltex Therapeutics Corporation 9/24/122/6www.fda.gov/ICECI/EnforcementActions/WarningLetters/2012/ucm323853.htm
Additionally, the clinical uses detailed in your protocols do not meet the definition of homologous use in 2CFR 1271.3(c). Also records collected during inspection indicate clinical uses of the AdMSC productinvolving
These uses would likely not be considered homologous use and as a result, the CellTexproduct does not meet the criterion in 21 CFR 1271.10(a) for regulation solely under section 361 of the PHAct and 21 CFR Part 1271. You are promoting the CellTex product in a manner that causes the product to be a drug under section201(g) of the FDC Act [21 U.S.C. 321(g)] and a biological product as defined in section 351(i) of the PHSAct [42 U.S.C. 262(i)]. Please be advised that in order to lawfully market such a biological drug product,valid biologics license must be in effect [21 U.S.C. 355(a); 42 U.S.C. 262(a)]. Such licenses are issuedonly after a showing of safety and efficacy for the product’s intended use. While in the development stage,for example, while being studied in a clinical investigation, such products may be used in humans only if the sponsor has an investigational new drug (IND) application in effect as specified by FDA regulations [21U.S.C. 355(i); 21 CFR Part 312]. The CellTex AdMSC product is not the subject of an approved biologicslicense application (BLA) nor is there an IND in effect. Based on this information, your product violates thFDC Act and the PHS Act.Additionally, during the inspection, FDA investigators documented evidence of significant deviations fromcurrent good manufacturing practice (CGMP) and current good tissue practice (CGTP) in the manufacture o
batches of your AdMSC product from July 2011 through April 2012. These deviations from CGMPand CGTP include the applicable requirements of Section 501(a)(2)(B) of the FDC Act, Sections 351(a) and361 of the PHS Act, and Title 21, Code of Federal Regulations, (21 CFR) Parts 210, 211, and 1271. At the close of the inspection, our investigators issued a Form FDA 483, Inspectional Observations, whichdescribed a number of significant objectionable conditions relating to your facility's compliance with CGMPand CGTP. These include, but are not limited to the following: 1. Failure to establish and follow written procedures designed to prevent microbiologicalcontamination of drug products purporting to be sterile. Such procedures shall include validation of all aseptic and sterilization processes [21 CFR 211.113(b)]. For example: a. The aseptic manufacturing process at your Sugarland, Texas facility has not been validated.b. You have not validated your aseptic gowning process and routine personnel monitoring is nperformed.c. You have not validated your autoclave sterilization cycle. The autoclave is used to sterilizeequipment used in aseptic processing.2. Failure to establish and follow written production and process control procedures designed toassure that the drug products have the identity, strength, quality, and purity they purport or arerepresented to possess and to assure such procedures are drafted, reviewed and approved by theappropriate organizational units [21 CFR 211.100(a)]. For example, you have failed to validate yourmanufacturing process at your Sugarland, Texas facility. 3. Failure to maintain laboratory controls that include the establishment of scientifically sound andappropriate specifications, standards, sampling plans, and test procedures designed to assure thatcomponents, drug product containers, closures, in-process materials, labeling, and drug productsconform to appropriate standards of identity, strength, quality, and purity [21 CFR211.160(b)]. Specifically, you do not perform testing of the final AdMSC product, including tests foridentity, safety, purity and potency.
4. Failure to test the AdMSC product, a
drug product, for the presence of 
although areasonable possibility exists that the
drug product has been exposed to cross contaminationwith
Your firm used
during culturing of your AdMSC product. Specifically,
wasused during manufacturing of the
batches of your AdMSC product reviewed. The
drugproduct must not be marketed if detectable levels of 
are found.5. Failure to thoroughly investigate any unexplained discrepancy or the failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already beendistributed [21 CFR 211.192]. For example, there were no investigations performed for the following a. There were numerous in-process sterility failures for AdMSC batches.
10/16/12 2012 > Celltex Therapeutics Corporation 9/24/123/6www.fda.gov/ICECI/EnforcementActions/WarningLetters/2012/ucm323853.htm
 b. Bacterial and fungal limits have been exceeded for the Biological Safety Cabinets (BSCs)used in manufacturing, and in the gowning and general areas. 6. Failure to assure all drug product production and control records, including those for packagingand labeling, are reviewed and approved by the quality control unit to determine compliance with allestablished, approved written procedures before the batch is released or distributed [21 CFR211.192]. There was no evidence of review and approval by the quality control unit prior to releaseof any of the
batches of your AdMSC product. 7. You failed to assure batch production and control records are prepared for each batch of drugproduct produced and that you document that each significant step in the manufacture, processing,packing, or holding of the batch was accomplished [21 CFR 211.188(b)]. For example: a. There is no documentation of the addition of 
to your final AdMSC product.b. There is no documentation of the personnel involved in packaging of the final AdMSCproduct. 8. Failure to assure that distribution records contain the name and strength of the product and thedescription of the dosage form, and the name and address of the consignee [21 CFR211.196]. Specifically, of the
batches reviewed, all were lacking a product name, dosageform, and the name and address of the consignee. 9. Failure to establish and follow written procedures describing in sufficient detail the receipt,identification, storage, handling, sampling, testing, and approval or rejection of components and druproduct containers and closures [21 CFR 211.80(a)]. Specifically, there are no written procedures inplace for the supplies and reagents you use to manufacture your AdMSC product at your Sugarland,Texas facility.10. Failure to assure that each lot of components, drug product containers, and closures shall bewithheld from use until the lot has been sampled, tested, or examined, as appropriate, and releasedfor use by the quality control unit [21 CFR 211.84(a)]. For example, the following components andcontainers are not tested or examined before release: a. The
used to rinse the cells and formulate the final drug product. More importantly,the Certificate of Analysis for the
states: “For in vitro diagnostic use. CAUTION: Not fohuman or animal therapeutic use. Uses other than the labeled intended use may be a violationof local law.” b. The
that contain the final product. 11. Failure to establish a written record of major equipment cleaning, maintenance and use toinclude in that record the date, time, product and lot number of each batch processed [21 CFR211.182]. For example, there are no written records of cleaning, maintenance and use for the
and BSCs used for aseptic processing or the refrigerators and freezers used to store
andreagents used to manufacture the AdMSC product.12. Failure to assure that automatic, mechanical and electronic equipment used in the manufacture,processing, packing and holding of a drug product is routinely calibrated, inspected or checkedaccording to a written program designed to assure proper performance, and that written records of those calibration checks and inspections are maintained [21 CFR 211.68(a)]. Specifically, there is nevidence that operational or performance qualification has been performed for your BSCs to assuretheir proper function. 13. Failure to assure an adequate control system for temperature and humidity is in place to prevencontamination during aseptic processing [21 CFR 211.42(c)(10)(ii)]. Specifically, there is no systemfor the monitoring of temperature or humidity of the processing rooms at your Sugarland, Texasfacility, where you manufacture the AdMSC product. The manufacturer's manual for your
BSCs states that they should be operated in environmental conditions of a maximum relativehumidity of 
 14. Failure to assure an air supply filtered through high-efficiency particulate air filters under

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